Journal
MOLECULAR IMAGING AND BIOLOGY
Volume 15, Issue 5, Pages 614-624Publisher
SPRINGER
DOI: 10.1007/s11307-013-0635-x
Keywords
Hollow gold nanospheres; Liver tumor; Intra-arterial injection; PET/CT; Copper-64; Lipiodol
Funding
- National Institutes of Health [CA119387, GM092599]
- John S. Dunn Research Foundation
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This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. Fifteen VX2 tumor-bearing rabbits were randomized into five groups (n = 3 in each group) that received either IV Cu-64-labeled PEG-HAuNS (IV-PEG-HAuNS), IA Cu-64-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated Cu-64-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated Cu-64-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA Cu-64-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 h after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 h after injection, and tissues were evaluated for radioactivity. At 1 h after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 h after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 h, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 vs. 0.099 %ID/g; P < 0.001). Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection.
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